A short double-stranded RNA, a microRNA (miRNA) and a small interfering RNA (siRNA) are an oligonucleotide containing a base sequence that is complementary to a target messenger RNA (mRNA). The target mRNA includes a base sequence of, for example, a gene responsible for a disease. RNA interference is defined as an in vivo gene inhibition mechanism in which a short double-stranded RNA, a miRNA and an siRNA inhibit expression of the gene of a target mRNA in vivo.
The siRNA is a double-stranded RNA which includes complementary base sequences. The siRNA combines with a target mRNA in a sequence specific manner. The siRNA combined with the target mRNA is incorporated into an RNA-induced silencing complex (RISC), so that the target mRNA is cut. If the base sequence of the gene responsible for a disease is apparent, it becomes possible to design and synthesize an siRNA which has a sequence complementary to the gene responsible for a disease. Therefore, the siRNA synthesized as described above can cut the gene responsible for a disease, and inhibit expression of a disease-related protein.
The miRNA is a double-stranded RNA which contains a partially mismatched base pair. The miRNA recognizes a target mRNA which partially has a complementary sequence, and combines with the target mRNA. When the miRNA combines with the target mRNA, the target mRNA is destabilized, thereby inhibiting translation of the target mRNA. As a result, expression of a gene is inhibited. It has been made clear that miRNA precisely control various biological functions such as generation, morphogenesis and cell growth of an organism. Recently, a pharmaceutical agent utilizing the RNA interference (a phenomenon of degrading an mRNA having a base sequence complementary to a double-stranded RNA) is actively studied. Especially, it is reported that the miRNA is associated with various diseases such as cancer.
For example, the expression amount of a let-7 miRNA is reduced in a lung cancer patient-derived cancer tissue. It has been reported that prognosis of a lung cancer patient can be determined by measuring the expression amount of the let-7 miRNA. Furthermore, it has been reported that the let-7 miRNA has proliferation-inhibiting effect on lung cancer (see Patent Document 1).